Objectives
The aim of the study was to assess changes in and factors associated with anatomical carotid artery intima‐media thickness (CIMT) and functional (arterial stiffness) markers of subclinical ...cardiovascular disease progression in antiretroviral‐naïve patients starting triple combination antiretroviral therapy containing contemporary protease inhibitors.
Methods
This was a planned substudy of the ATADAR (Metabolic Effects of Atazanavir/Ritonavir Versus Darunavir/Ritonavir in Combination With Tenofovir/Emtricitabine in naïve HIV‐1 Infected Patients) clinical trial (ClinicalTrials.gov identifier NCT01274780). ATADAR is a multicentre, randomized, open‐label clinical trial comparing the effects of ritonavir‐boosted atazanavir and darunavir, both with tenofovir/emtricitabine, in antiretroviral‐naïve HIV‐infected patients. Common CIMT and aortic augmentation index (AIx@75) were measured at baseline and after 12 months of follow‐up. Antiretroviral treatment, traditional cardiovascular risk factors and HIV‐related factors were assessed as potential predictors of CIMT and Aix@75 changes using linear regression analysis.
Results
Thirty‐three patients were included in this pilot study. While CIMT significantly increased in the pooled population median (interquartile range (IQR)) 68 (−13, 128) μm; P = 0.0511, AIx@75 did not median (IQR) 1 (−6, 5)%; P = 0.8964. Patients on darunavir showed a trend to faster CIMT progression than those on atazanavir median change (IQR) 117 (−2, 143) vs. −6 (−58, 89) μm, respectively; P = 0.0917. However, after adjustment in the multivariate analysis, a higher baseline Framingham score was the only factor associated with CIMT progression (coefficient 16.02; 95% confidence interval –1.04, 33.08; P = 0.064). AIx@75 change was not associated with any baseline factor.
Conclusions
CIMT was a more sensitive marker of subclinical vascular disease progression than arterial stiffness in antiretroviral‐naïve patients starting antiretroviral therapy with contemporary protease inhibitors. Classical risk factors but not antiretroviral therapy were associated with faster CIMT progression.
Abstract
Background
The incidence of non-AIDS defining cancer (NADC) is higher in people living with HIV (PLWH) than in the general population, and it is already one of the leading causes of death in ...the HIV-infected population. It is estimated that the situation will be aggravated by the progressive aging of PLWH. Early diagnosis through intensive cancer screening may improve the ability for therapeutic interventions and could be critical in reducing mortality, but it might also increase expenditure and harms associated with adverse events. The aim of this study is to evaluate an enhanced screening program for early diagnosis of cancer in PLWH compared to standard practice. The specific objectives are (1) to compare the frequency of cancer diagnosed at an early stage, (2) to analyze safety of the enhanced program: adverse events and unnecessary interventions, (3) to analyze the cost-utility of the program, and (4) to estimate the overall and site-specific incidence of NADC in PLWH.
Methods
We will conduct a multicenter, non-blinded, randomized, controlled trial, comparing two parallel arms: conventional vs enhanced screening. Data will be recorded in an electronic data collection notebook. Conventional intervention group will follow the standard of care screening in the participating centers, according to the European AIDS Clinical Society recommendations, and the enhanced intervention group will follow an expanded screening aimed to early detection of lung, liver, anal, cervical, breast, prostate, colorectal, and skin cancer. The trial will be conducted within the framework of the Spanish AIDS Research Network Cohort (CoRIS).
Discussion
The trial will evaluate the efficacy, safety, and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard of care practice. The information provided will be relevant since there are currently no studies on expanded cancer screening strategies in patients with HIV, and available data estimating cost effectiveness or cost-utility of such as programs are scarce. An enhanced program for NADC screening in patients with HIV could lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions, but it is critical to demonstrate that the benefits clearly outweigh the harms, before the strategy could be implemented.
Trial registration
ClinicalTrials.gov
NCT04735445. Registered on 25 June 2019
Background
Patients with a discordant response to cART, defined as persistent CD4 + T‐cell counts <200 cells/mm3 and lack CD4 increase despite virologic suppression on HAART, have an increased risk ...of morbidity and mortality. Several studies have suggested a potential benefit of intensification with maraviroc (MVC) on CD4+T‐cell recovery.
Methods
A 24‐week prospective, open‐label, randomized, controlled study. Subjects on cART, plasma HIV RNA <37 copies/mL for at least 12 months, and CD4 < 200 cells/L, with CD4‐gain in the previous 12 months <50 cells/µL, were randomized to add MVC (A) or continuing same cART (B). Randomisation was stratified by the presence of liver cirrhosis (CH) (n = 10) and non‐CH (n = 28). We measured by flow cytometry changes in the following parameters of CD4 + and CD8 + T‐cell subsets: activation (CD38, HLA‐DR), senescence (CD28, CD57, CD45RA and RO), coreceptors (CCR5 and CXCR4) and apoptosis (Annexin‐V).
Results
Thirty‐eight subjects were included at the final analysis. Median values were: age 51 years (IQR, 44–57), time with VL < 37 copies/mL before entry 43 months (IQR 24–62 months), baseline CD4 + T‐cell count 144 cells/µL (IQR 106–181). Four subjects were lost of follow‐up (3 in A, 1 in B). One subject from group B experienced confirmed virologic failure at week 24. Adverse events were similar in both arms. Median increase in CD4 + T‐cell count from baseline to weeks 2,4 and 24 in both groups were +15.5 vs ‐1 (p = 0.025); +16.5 vs ‐2.5 (p = 0.158); +46.5 vs + 6.50 (p = 0.190). Similar trend towards a higher CD4 increase were seen in both CH and non‐CH individuals. At W24, 8 subjects from arm A vs 1 subject from arm B achieved a CD4 + T‐cell count above 200 cells/µL (p < 0.05). Markers of immune activation (CD38 and HLA‐DR) decreased during MVC intensification, especially in CD8+ T cells (p < 0.01) whereas apoptosis did not. Additionally CCR5 expression tended to increase (p = 0.051) in CD8 T cells from arm A subjects. No significant differences were found in the immunological assay between cirrhotic and non cirrhotic individuals.
Conclusions
MVC intensification was safe and was associated with a significant a trend towards increasing CD4 + T‐cell counts both in cirrhotic as well as non‐cirrhotic patients with discordant response. The addition of MVC was associated with a decrease in markers of immune activation in both groups.
Purpose of the study
ATV/r or DRV/r plus TDF/FTC are recommended for first‐line therapy due at least in part to their clinical tolerability and scarce metabolic effects. We investigated whether both ...regimens might differ regarding plasma lipids, insulin resistance (HOMA‐IR), and estimated glomerular filtration rate (MDRD).
Methods
Multicentre, randomized, clinical trial (ATADAR Study, NCT01274780). Primary end‐point: 24‐week change in total cholesterol. Secondary end‐points: changes in lipids other than total cholesterol, HOMA‐IR, and MDRD; clinical tolerability; and efficacy. We assumed that patients assigned to DRV/r would have an increase in plasma total cholesterol<21 mg/dL, which was the difference between lopinavir/r and ATV/r in CASTLE study. Fasting plasma lipids, glucose, insulin, and creatinine were measured at baseline, and 4, 12, and 24 weeks. Analyses were by intent‐to‐treat.
Summary of results
180 patients were randomized (ATV/r=91, DRV/r=89), 95% Caucasian, and 8% co‐infected with hepatitis C virus. At baseline (mean, SD): age 36 (9) years; plasma log HIV RNA 4.8 (0.7); CD4 334 (189) cells/mm3; triglycerides 107 (62), total cholesterol 158 (32), LDL cholesterol 97 (28), HDL cholesterol 39 (11) mg/dL, and glucose 84 (13) mg/dL; HOMA‐IR 2.47 (3.46); and MDRD 108 (21) mL/min/1.73 m2. At 24 weeks, total cholesterol (mean, SD) changed +7.26 (26.76) mg/dL with ATV/r and +11.47 (25.85) mg/dL with DRV/r (estimated difference ATV/r minus DRV/r −4.21 (95% CI−12.11 to +3.69), P=0.2944), thus confirming our primary hypothesis. Changes (mean, SD) in triglycerides were roughly similar: +16.29 (61.76) mg/dL with ATV/r and +18.40 (64.24) mg/dL with DRV/r (P=0.8261), but there were trends to more favourable changes in LDL (−2.14 21.45 vs +3.14 21.97 mg/dL, P=0.1160) and HDL cholesterol (+5.50 10.36 vs +3.88 8.42 mg/dL, P=0.2625), and total‐to‐HDL cholesterol ratio (−1.16 6.38 vs −0.14 0.86, P=0.0652) with ATV/r than with DRV/r. There were small, non‐significant decreases in HOMA‐IR (ATV/r −0.17 2.48 vs DRV/r −0.70 3.38, P=0.3785) and MDRD (ATV/r −7 22 vs DRV/r −6 15 mL/min/1.73 m2, P=0.6652). 6 ATV/r and 3 DRV/r patients had their study drugs discontinued because of adverse effects (P=0.4967). 7 additional patients in each arm had confirmed HIV RNA >50 copies.
Conclusions
There were trends to more favourable changes in LDL and HDL cholesterol and particularly total‐to‐HDL cholesterol ratio at 24 weeks with ATV/r than with DRV/r.
Background
Simplification of antiretroviral therapy (ART) may be an option for virologically suppressed patients for a variety of reasons. Etravirine (ETV) 400 mg qd has a good safety profile and ...retains activity against viruses resistant to nevirapine or efavirenz. Our objective was to evaluate the efficacy of ETV plus two nucleoside reverse transcriptase inhibitors (NRTIs) as a simplification strategy in treatment‐experienced virologically suppressed individuals with prior episodes of virological failure (VF) and presence of genotypic resistance mutations (GRM).
Methods
Eligible subjects were followed for ≥6 mo. Primary endpoint was proportion of patients remaining virologically suppressed using an ITT analysis. Genotypic sensitivity score (GSS) to new regimen was calculated according to Stanford resistance database.
Results
Fourteen (10%) of 145 subjects switching to ETV+2NRTIs while virologically suppressed had a documented prior VF and presence of GRM and were included in the analysis. Median (range) number of previous episodes of VF to ART, NRTI‐containing regimen, to a NNRTI‐containing regimen and to a PI‐containing regimen were 4 (1–6), 2 (1–5), 1 (0–2) and 1 (0–2) respectively. Median duration of virological suppression before switching therapy was 22.5 months (1‐65). All patients switched from an effective PI‐containing regimen (8 LPV/r, 5 ATV/r and 1 DRV/r) to a qd regimen with ETV 400 mg plus Truvada® (n=12) or Kivexa® (2). 11/14 patients (79%) remained virologically suppressed at ≥6 mo. All of them had a GSS >1.5 to the new regimen and none had resistance to etravirine. Conversely 3/14 (21%) developed a VF at 1, 3 and 6 months respectively. All these 3 patients had a GSS ≤1.5 to the new regimen and 2 of them intermediate resistance to ETV (Y181C). No side effects were reported.
Conclusions
Our results suggest that ETV plus 2NRTI could be a good strategy for simplification in virologically suppressed patients despite previous episodes of VF if the GSS to the new regimen is ≥1.5 and ETV remains active.
Abstract Background The number of consultations for sexually transmitted infections (STIs) is increasing in Spain. The aim of this study was to describe and analyze the epidemiological, behavioral, ...clinical, and microbiological characteristics of patients registered at the STI unit of a tertiary hospital. Methods This was a retrospective, single-center descriptive study carried out between 2010 and 2013 in a multidisciplinary unit specialized in STIs, situated in a tertiary hospital. Epidemiological, clinical, and behavioral data were gathered using a face-to-face interview and a standardized questionnaire. Samples were collected for microbiology analysis. Results The study included 546 patients: 96% were men, 41% had human immunodeficiency virus (HIV) infection, and 56% were men who have sex with men. The reasons for consultation were the following: urethritis; genital, anal, or perianal ulcers; proctitis; oral ulcers; sexual contact with a person with a known STI; and high-risk sexual contact. The most common microbiological diagnoses were Neisseria gonorrhoeae in urethritis, Treponema pallidum in genital and anal or perianal ulcers, and Chlamydia trachomatis lymphogranuloma venereum serovars in proctitis. The highest prevalences of the main STIs studied occurred in homosexual men with HIV infection. Conclusion This study confirms the increase in the incidence of STIs in recent years and the epidemiological characteristics of the HIV/STI epidemic in Spain.
To assess HIV-1 post-exposure prophylaxis (PEP) non-completion at day 28, comparing ritonavir-boosted lopinavir versus cobicistat-boosted elvitegravir as a single-tablet regimen (STR), using ...tenofovir disoproxil fumarate/emtricitabine with both of these therapies.
A prospective, open, randomized clinical trial was performed. Individuals attending the emergency room due to potential sexual exposure to HIV and who met criteria for PEP were randomized 1:3 into two groups receiving either 400/100 mg of lopinavir/ritonavir (n = 38) or 150/150 mg of elvitegravir/cobicistat (n = 119), with both groups also receiving 245/200 mg of tenofovir disoproxil fumarate/emtricitabine. Five follow-up visits were scheduled at days 1, 10, 28, 90 and 180. The primary endpoint was PEP non-completion at day 28. Secondary endpoints were adherence, adverse effects and rate of seroconversions. Clinical trials.gov number: NCT08431173.
Median age was 32 years and 95% were males. PEP non-completion at day 28 was 36% (n = 57), with a trend to be higher in the lopinavir/ritonavir arm lopinavir/ritonavir 47% (n = 18) versus elvitegravir/cobicistat 33% (n = 39), P = 0.10. We performed a modified ITT analysis including only those patients who attended on day 1. PEP non-completion in this subgroup was higher in the lopinavir/ritonavir arm than in the elvitegravir/cobicistat arm (33% versus 15%, respectively, P = 0.04). Poor adherence was significantly higher in the lopinavir/ritonavir arm versus the elvitegravir/cobicistat arm (47% versus 9%, respectively, P < 0.0001). Adverse events were reported by 73 patients (59%), and were significantly more common in the lopinavir/ritonavir arm (90% versus 49%, P = 0.0001). A seroconversion was observed in the elvitegravir/cobicistat arm in a patient with multiple exposures before and after PEP.
A higher PEP non-completion, poor adherence and adverse events were observed in patients allocated to the lopinavir/ritonavir arm, suggesting that STR elvitegravir/cobicistat is a well-tolerated antiretroviral for PEP.
Abstract
Background
The use of remdesivir has demonstrated a significant reduction in the time to recovery in patients with COVID-19. However, the impact on mortality is still controversial. ...Therefore, it is necessary to evaluate whether there is a specific subgroup of patients in whom an active antiviral therapy also reduces the mortality.
Methods
Patients admitted for >48 h in our hospital for a SARS-CoV-2 confirmed or suspected infection from February 2020 to February 2021 were retrospectively analysed. The primary outcome of the study was mortality at 30 days. Univariate and multivariate analyses were performed to identify predictors of mortality.
Results
In total, 2607 patients (438 receiving remdesivir and 2169 not) were included with a median (IQR) age of 65 (54–77) years and 58% were male. Four hundred and seventy-six were admitted to the ICU (18.3%) and 264 required invasive mechanical ventilation (10.1%). The global 30 day mortality rate was 10.7%. Pre-admission symptom duration of 4–6 days and ≤3 days was associated with a 1.5- and 2.5-fold increase in the mortality rate, respectively, in comparison with >6 days and treatment with remdesivir was independently associated with a lower mortality rate (OR = 0.382, 95% CI = 0.218–0.671). The analysis showed that the major difference was among patients with shorter pre-admission symptom duration (<6 days).
Conclusions
Patients with ≤3 days and 4–6 days from symptom onset to admission are associated with a 2.5- and 1.5-fold higher risk of death, respectively. Remdesivir was associated with 62% reduced odds of death versus standard-of-care and its survival benefit increased with shorter duration of symptoms.
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